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Single Cell Transcriptomics-Informed Induced Pluripotent Stem Cells Differentiation to Tenogenic Lineag

GSE285276 Homo sapiens Expression profiling by high throughput sequencing 7 samples Submitted 2024/12/24 Platform GPL24676
Summary
During vertebrate embryogenesis, axial tendons develop from the paraxial mesoderm and differentiate through specific developmental stages to reach the syndetome stage. While the main roles of signaling pathways in the earlier stages of the differentiation have been well established, pathway nuances in syndetome specification from the sclerotome stage have yet to be explored. Here, we show stepwise differentiation of human iPSCs to the syndetome stage using chemically defined media and small molecules that were modified based on single cell RNA-sequencing and pathway analysis. We identified a significant population of branching off-target cells differentiating towards a neural phenotype overexpressing Wnt. Further transcriptomics post-addition of a WNT inhibitor at the somite stage and onwards revealed not only total removal of the neural off-target cells, but also increased syndetome induction efficiency. Fine-tuning tendon differentiation in vitro is essential to address the current challenges in developing a successful cell-based tendon therapy.
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Direct links to NCBI, no account and no request form: the whole study as GSE285276_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 7 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1202147 and SRA study SRP589910. Searching any of these in the dataset finder brings you back here.

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